U.S. patent application number 17/478878 was filed with the patent office on 2022-06-16 for cell separation apparatus for bioreactor.
This patent application is currently assigned to SHANGHAI AIZHONG BIOTECHNOLOGY CO., LTD.. The applicant listed for this patent is SHANGHAI AIZHONG BIOTECHNOLOGY CO., LTD.. Invention is credited to Rui CHEN, Yu LIU.
Application Number | 20220186173 17/478878 |
Document ID | / |
Family ID | 1000005851159 |
Filed Date | 2022-06-16 |
United States Patent
Application |
20220186173 |
Kind Code |
A1 |
LIU; Yu ; et al. |
June 16, 2022 |
CELL SEPARATION APPARATUS FOR BIOREACTOR
Abstract
The present disclosure provides a cell separation apparatus for
a bioreactor. The cell separation apparatus may be disposed outside
the bioreactor and in fluid connection with the bioreactor, the
cell separation apparatus may be in a shape of a box body, the cell
separation apparatus may include a liquid buffer device including a
first liquid cavity disposed in the box body; a filter device
including a filter channel and a filter membrane disposed in the
box body, the filter membrane may be disposed above the filter
channel; and a first liquid channel may be configured in the box
body to facilitate a fluid communication between the first liquid
cavity and the filter channel. A power system for filtering and
microfluidic channels are integrated in the cell separation
apparatus that is of a box shape, thereby reducing the volume and
production cost thereof.
Inventors: |
LIU; Yu; (Shanghai, CN)
; CHEN; Rui; (Shanghai, CN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
SHANGHAI AIZHONG BIOTECHNOLOGY CO., LTD. |
Shanghai |
|
CN |
|
|
Assignee: |
SHANGHAI AIZHONG BIOTECHNOLOGY CO.,
LTD.
Shanghai
CN
|
Family ID: |
1000005851159 |
Appl. No.: |
17/478878 |
Filed: |
September 18, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
17198291 |
Mar 11, 2021 |
|
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17478878 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C12M 41/40 20130101;
B01D 69/10 20130101; B01D 2313/086 20130101; B01D 63/087 20130101;
B01D 2319/02 20130101; C12M 47/02 20130101; B01D 65/10 20130101;
B01D 63/082 20130101; B01D 2313/243 20130101; C12M 29/00 20130101;
B01D 69/06 20130101; B01D 63/088 20130101 |
International
Class: |
C12M 1/00 20060101
C12M001/00; B01D 63/08 20060101 B01D063/08; B01D 69/10 20060101
B01D069/10; B01D 65/10 20060101 B01D065/10; C12M 1/34 20060101
C12M001/34; B01D 69/06 20060101 B01D069/06 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 10, 2020 |
CN |
202011434563.3 |
Claims
1. A cell separation apparatus for a bioreactor, the cell
separation apparatus being in fluid connection with the bioreactor,
the cell separation apparatus being in a shape of a box body, the
cell separation apparatus comprising: a liquid buffer device
including a first liquid cavity disposed in the box body; and a
filter device including a filter channel and a filter membrane
disposed in the box body, the filter membrane being disposed above
the filter channel, the filter membrane including a single layer or
stacked multiple layers; a power device fixed to the box body;
wherein a first liquid channel is disposed in the box body to
facilitate liquid in the first liquid cavity to flow to the filter
channel for filtering, and the first liquid cavity is in gaseous
communication with the power device.
2. (canceled)
3. The cell separation apparatus of claim 2, wherein the power
device includes a syringe pump or an air cylinder.
4. The cell separation apparatus of claim 1, wherein a volume ratio
of the first liquid cavity to the bioreactor is 0.01-0.8.
5. The cell separation apparatus of claim 1, wherein the box body
includes a stacked layer, and the stacked layer includes a first
shell plate, a membrane layer, a support plate, and a second shell
plate.
6. The cell separation apparatus of claim 5, wherein the first
liquid cavity is fixed to an outer end surface of the stacked
layer.
7. The cell separation apparatus of claim 5, wherein the first
liquid channel is recessed from an inner surface of the first shell
plate, and a top of the first liquid channel is covered and sealed
by a sealing film in the membrane layer.
8. The cell separation apparatus of claim 7, wherein a pressure
sensor is configured in the first liquid channel to monitor a
clogging state of the filter device.
9. The cell separation apparatus of claim 7, wherein the first
liquid channel is configured on the first shell plate through at
least one of machining, laser etching, or soft plastic injection
molding.
10. The cell separation apparatus of claim 5, wherein the liquid
buffer device further comprises a second liquid cavity disposed in
the box body, a second liquid channel is configured in the box body
to facilitate a fluid communication between the second liquid
cavity and the filter channel.
11. The cell separation apparatus of claim 10, wherein the second
liquid cavity is fixed to an outer end surface of the stacked
layer.
12. The cell separation apparatus of claim 10, wherein the second
liquid cavity is in gaseous communication with the power
device.
13. The cell separation apparatus of claim 10, wherein a third
liquid channel is configured in the box body to facilitate a fluid
communication between the first liquid cavity and the bioreactor,
and a fourth liquid channel is disposed in the box body to
facilitate a fluid communication between the second liquid cavity
and the bioreactor.
14. The cell separation apparatus of claim 13, wherein the first
liquid channel, the second liquid channel, the third liquid
channel, and the fourth liquid channel are recessed from an inner
surface of the first shell, and a top of the first liquid channel,
a top of the second liquid channel, a top of the third liquid
channel, and a top of the fourth liquid channel are covered and
sealed by a sealing film in the membrane layer.
15. The cell separation apparatus of claim 13, wherein one or more
pressure sensors are configured in the first liquid channel and/or
the third liquid channel to monitor a clogging state of the filter
device.
16. The cell separation apparatus of claim 13, wherein the first
liquid channel, the second liquid channel, the third liquid
channel, and/or the fourth liquid channel are configured on the
first shell plate through at least one of machining, laser etching,
or soft plastic injection molding.
17. The cell separation apparatus of claim 5, wherein the filter
channel is recessed from an inner surface of the first shell plate,
and a top of the filter channel is covered by the filter membrane
in the membrane layer.
18. The cell separation apparatus of claim 17, wherein an
arrangement pattern of the filter channel on the first shell plate
is of a coiled shape.
19. The cell separation apparatus of claim 1, wherein the filter
channel is configured as a single filter channel, and an outlet of
the single filter channel is closed or the single filter channel
forms a closed loop.
20. The cell separation apparatus of claim 1, wherein the filter
channel is configured as a plurality of filter channels connected
in parallel, and an outlet of each filter channel of the plurality
of filter channels is closed or the each filter channel forms a
closed loop.
21. The cell separation apparatus of claim 5, wherein the cell
separation apparatus further comprises an inlet valve disposed in
the first liquid channel, and the inlet valve includes a valve body
cavity and a spool cavity, wherein the valve body cavity is
recessed from an inner surface of the first shell plate, and a top
of the valve body cavity is covered and sealed by a sealing film in
the membrane layer.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 17/198,291, filed Mar. 11, 2021, which claims
priority of Chinese Patent Application No. 202011434563.3, filed on
Dec. 10, 2020, the contents of which are hereby incorporated by
reference.
TECHNICAL FIELD
[0002] The present disclosure generally relates to the field of
bioreactors, and in particular, to a cell separation apparatus for
a bioreactor.
BACKGROUND
[0003] In a design of animal cell bioreactors, more and more
processes involve a separation of cells from a culture fluid or
other solutions. These processes include perfusion culturing, fluid
exchanging or cell cleaning. Traditional separation apparatuses
include an alternating tangential flow filtration (ATF) system, a
tangential flow filtration (TFF) system, etc. These systems use a
centrifugal pump or a diaphragm pump to provide power and pump a
mixture of cells and a culture fluid to a hollow fiber column, and
use fiber pores of the hollow fiber column to separate cells and
the culture fluid.
[0004] Some systems use a centrifugal pump to provide power for
pumping the mixture of cells and the culture fluid. However, the
centrifugal pump has a disadvantage of, for example, an excessive
shear force. Animal cells (especially human T cells or stem cells)
are very sensitive to the shear force. An excessive shear force may
cause the oncogenesis of stem cells or loss of cell markers,
thereby seriously affecting the safety of cell therapy products.
Some systems use a diaphragm pump to provide power for pumping the
mixture of cells and the culture fluid. However, the diaphragm pump
has a disadvantage of, for example, non-linear pressurization of
liquid in pipeline. Non-linear pressurization can lead to a
relatively large fluctuation of an instantaneous pressure in a
culture system, which brings one or more potential effects to the
stability of the process.
[0005] In actual use of bioreactors, the hollow fiber column used
for the separation of cells and culture fluids is not only
expensive, but also too large (e.g., for the ATF2 system of
XCell.TM., a 2 L-10 L bioreactor requires a 60 cm high hollow fiber
column), and thus is not suitable for small disposable cell
separation apparatuses. In addition, multiple pipe connections are
required between the hollow fiber column and the bioreactor, and
accordingly, assembly and disassembly operations thereof are
complicated.
SUMMARY
[0006] According to an aspect of the present disclosure, a cell
separation apparatus that can overcome at least one defect in the
prior art is provided.
[0007] The subject technology of the present disclosure is
explained in terms of various aspects described below. For
convenience, various examples of various aspects of the subject
technology are described as labeled terms (1, 2, 3, etc.). These
terms are provided as examples, rather than limiting the subject
technology of this disclosure.
[0008] In one aspect of the present disclosure, a cell separation
apparatus for a bioreactor is provided. The cell separation
apparatus may be disposed outside the bioreactor and in fluid
connection with the bioreactor, the cell separation apparatus may
be in a shape of a box body, the cell separation apparatus may
comprise.
[0009] a liquid buffer device including a first liquid cavity
disposed in the box body; and
[0010] a filter device including a filter channel and a filter
membrane disposed in the box body, the filter membrane being
disposed above the filter channel.
[0011] wherein a first liquid channel may be configured in the box
body to facilitate a fluid communication between the first liquid
cavity and the filter channel.
[0012] In some embodiments, the cell separation apparatus may
further comprise a power device fixed to the box body, and the
first liquid cavity may be in gaseous communication with the power
device.
[0013] In some embodiments, the power device may include a syringe
pump or an air cylinder.
[0014] In some embodiments, a volume of the first liquid cavity may
be 0.01-0.8 bioreactor culture volume.
[0015] In some embodiments, the box body may include a stacked
layer, and the stacked layer may include a first shell plate, a
membrane layer, a support plate, and a second shell plate.
[0016] In some embodiments, the first liquid cavity may be fixed to
an outer end surface of the stacked layer.
[0017] In some embodiments, the first liquid channel may be
recessed from an inner surface of the first shell plate, and a top
of the first liquid channel may be covered and sealed by a sealing
film in the membrane layer.
[0018] In some embodiments, a pressure sensor may be configured in
the first liquid channel to monitor a clogging state of the filter
device.
[0019] In some embodiments, the first liquid channel may be
configured on the first shell plate through at least one of
machining, laser etching, or soft plastic injection molding.
[0020] In some embodiments, a cross section of the first liquid
channel perpendicular to the first shell plate may be of a shape of
a semicircle or rectangle, and a diameter or a side length of the
first liquid channel may be in a range from 0.01 mm to 2 mm.
[0021] In some embodiments, a diameter or a side length of the
first liquid channel may be in a range from 0.1 mm to 1 mm.
[0022] In some embodiments, the liquid buffer device may further
comprise a second liquid cavity disposed in the box body, a second
liquid channel may be disposed in the box body to facilitate a
fluid communication between the second liquid cavity and the filter
channel.
[0023] In some embodiments, the second liquid cavity may be fixed
to an outer end surface of the stacked layer.
[0024] In some embodiments, the second liquid cavity may be in
gaseous communication with the power device.
[0025] In some embodiments, a volume of the second liquid cavity
may be 0.01-0.8 bioreactor culture volume.
[0026] In some embodiments, a third liquid channel may be
configured in the box body to facilitate a fluid communication
between the first liquid cavity and the bioreactor, and a fourth
liquid channel may be configured in the box body to facilitate a
fluid communication between the second liquid cavity and the
bioreactor.
[0027] In some embodiments, the first liquid channel, the second
liquid channel, the third liquid channel, and the fourth liquid
channel may be recessed from an inner surface of the first shell,
and a top of the first liquid channel, a top of the second liquid
channel, a top of the third liquid channel, and a top of the fourth
liquid channel may be covered and sealed by a sealing film in the
membrane layer.
[0028] In some embodiments, one or more pressure sensors may be
configured in the first liquid channel and/or the third liquid
channel to monitor a clogging state of the filter device.
[0029] In some embodiments, the first liquid channel, the second
liquid channel, the third liquid channel, and/or the fourth liquid
channel may be configured on the first shell plate through at least
one of machining, laser etching, or soft plastic injection
molding.
[0030] In some embodiments, a cross section perpendicular to the
first shell plate of the first liquid channel, the second liquid
channel, the third liquid channel, and/or the fourth liquid channel
may be of a shape of a semicircle or rectangle, and a diameter or a
side length of the first liquid channel, the second liquid channel,
the third liquid channel, and/or the fourth liquid channel may be
in a range from 0.01 mm to 2 mm.
[0031] In some embodiments, a diameter or a side length of the
first liquid channel, the second liquid channel, the third liquid
channel, and/or the fourth liquid channel may be in a range from
0.1 mm to 1 mm.
[0032] In some embodiments, the first liquid channel, the second
liquid channel, the third liquid channel, and the fourth liquid
channel may be equipped with a valve.
[0033] In some embodiments, the value may include a valve body
cavity and a spool cavity that are in fluid communication, and the
valve body cavity may be disposed in a corresponding liquid
channel.
[0034] In some embodiments, the valve body cavity may be recessed
from an inner surface of the first shell plate, and a top of the
valve body cavity may be covered and sealed by a sealing film in
the membrane layer.
[0035] In some embodiments, a cross section of the valve body
cavity perpendicular to the first shell plate may be larger than a
cross section of a corresponding liquid channel.
[0036] In some embodiments, a cross section of the valve body
cavity perpendicular to the first shell plate may be of a circular,
oval, square, or rectangular shape.
[0037] In some embodiments, the valve body cavity may be configured
on the first shell plate through at least one of machining, laser
etching, or soft plastic injection molding.
[0038] In some embodiments, the spool cavity may be a through
cavity disposed on the support plate and the second shell plate,
and the position of the spool cavity may correspond to the valve
body cavity.
[0039] In some embodiments, the cell separation apparatus may
further include an additional power device fixed to the box body,
and the spool cavity may be in fluid communication with the
additional power device.
[0040] In some embodiments, the additional power device may be
configured to push the gas into the spool cavity to generate a
positive pressure in the spool cavity, and make the sealing film
seal the valve body cavity to close a corresponding liquid channel.
The additional power device may be further configured to suction
the gas out from the spool cavity to generate a negative pressure
in the spool cavity, and make the sealing film release the valve
body cavity to open the corresponding liquid channel.
[0041] In some embodiments, the additional power device may be
configured to push the spool into the valve body cavity, and make
the sealing film seal the valve body cavity to close a
corresponding liquid channel. The additional power device may be
further configured to push the spool to leave the valve body
cavity, and make the sealing film release the valve body cavity to
open the corresponding liquid channel.
[0042] In some embodiments, the filter channel may be recessed from
an inner surface of the first shell plate, and a top of the filter
channel may be covered by the filter membrane in the membrane
layer.
[0043] In some embodiments, the filter channel may be configured on
the first shell plate through at least one of machining, laser
etching, or soft plastic injection molding.
[0044] In some embodiments, a cross section of the filter channel
perpendicular to the first shell plate may be of a shape of a
semicircle or rectangle, and a diameter or a side length of the
filter channel may be in a range from 0.01 mm to 2 mm.
[0045] In some embodiments, a diameter or a side length of the
filter channel may be in a range from 0.1 mm to 1 mm.
[0046] In some embodiments, an arrangement pattern of the filter
channel on the first shell plate may be of a coiled shape.
[0047] In some embodiments, the filter channel may be configured as
a single filter channel, and an outlet of the single filter channel
may be closed or the single filter channel may form a closed
loop.
[0048] In some embodiment, the filtering channel may be configured
as a plurality of filter channels connected in parallel, and an
outlet of each filter channel of the plurality of filter channels
may be closed or the each filter channel may form a closed
loop.
[0049] In some embodiments, each filter channel of the plurality of
filter channels may be equipped with a valve.
[0050] In some embodiments, the filter membrane may be configured
as a single layer or stacked multiple layers.
[0051] In some embodiments, the filter membrane may be made of a
material including PTFE, PP, PC, nylon, PES, PVDF, or a sintered
porous material.
[0052] In some embodiments, the filter membrane may adopt a pore
size of 0.2 .mu.m, 1 .mu.m, 4 .mu.m, 5 .mu.m, 10 .mu.m, 20 .mu.m,
50 .mu.m, and/or 200 .mu.m.
[0053] In some embodiments, the filter membrane may be supported by
the support plate to increase the strength of the filter membrane
when the liquid presses the filter membrane.
[0054] In some embodiments, the support plate may be made of a
material including PS, PMMA, PETG, or PET.
[0055] In some embodiments, the filter device may further include a
collection chamber configured to collect the liquid flowing through
the filter membrane.
[0056] In some embodiments, the support plate may be equipped with
a plurality of through holes on a site corresponding to the filter
channel, the collection chamber may be recessed from an inner
surface of the second shell plate, and a position of the collection
chamber corresponds to the plurality of through holes on the
support plate.
[0057] In some embodiments, the collection chamber may be connected
to the outside of the cell separation apparatus through a return
conduit.
[0058] In some embodiments, a peristaltic pump or a pinch valve may
be disposed on the return conduit to control a flow rate of the
liquid backwashing the filter membrane.
[0059] In some embodiments, a length of the box body may be in a
range from 1 cm to 8 cm, a width of the box body may be in a range
from 1 cm to 15 cm, and a height of the box body may be in a range
from 1 cm to 15 cm.
[0060] In some embodiments, the first liquid cavity and the second
liquid cavity may be configured such that when a valve of the third
liquid channel is open and a valve of the first liquid channel is
closed, a gas can be suctioned from the first liquid cavity, and
thus, the liquid in the bioreactor may be suctioned to the first
liquid cavity through the third liquid channel. When a valve of the
fourth liquid channel is closed and a valve of the second liquid
channel is open, the gas can be suctioned to the second liquid
cavity, and thus, the liquid in the second liquid cavity may leave
the second liquid cavity, and be pushed to the filter device
through the second liquid channel.
[0061] In some embodiments, the first liquid cavity and the second
liquid cavity may be configured such that when a valve of the third
liquid channel is closed and a valve of the first liquid channel is
open, a gas can be pushed to the first liquid cavity, and thus, the
liquid in the first liquid cavity may leave the first liquid
cavity, and be pushed to the filter device through the first liquid
channel. When a valve of the fourth liquid channel is open and a
valve of the second liquid channel is closed, the gas can be
suctioned from the second liquid cavity, and thus, the liquid in
the bioreactor may be suctioned to the second liquid cavity through
the fourth liquid channel.
[0062] Additional features will be set forth in part in the
description which follows, and in part will become apparent to
those skilled in the art upon examination of the following and the
accompanying drawings or may be learned by production or operation
of the examples. The features of the present disclosure may be
realized and attained by practice or use of various aspects of the
methodologies, instrumentalities, and combinations set forth in the
detailed examples discussed below.
[0063] It should be understood that the foregoing general
description and the following detailed description are both
exemplary and illustrative, and are intended to provide a further
description of the subject technology of the claimed
disclosure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0064] Based on the following specific embodiments and the
drawings, various aspects of the present disclosure will be better
understood. In the drawings:
[0065] FIG. 1 is a schematic diagram illustrating a disposable cell
separation apparatus;
[0066] FIG. 2 is a schematic diagram illustrating usage of the
disposable cell separation apparatus according to a first
embodiment of the present disclosure;
[0067] FIGS. 3A and 3B are schematic diagrams illustrating
connections of components of the disposable cell separation
apparatus shown in FIG. 2;
[0068] FIGS. 4A and 4B show an exploded stereogram and an exploded
perspective view illustrating the disposable cell separation
apparatus shown in FIG. 2, FIG. 4C is an exploded perspective view
illustrating the disposable cell separation apparatus without
related power device.
[0069] FIGS. 5A and 5B are schematic diagrams illustrating an
example of a valve of the disposable cell separation apparatus
shown in FIG. 2;
[0070] FIGS. 6A and 6B are schematic diagrams illustrating another
example of the valve of the disposable cell separation apparatus
shown in FIG. 2;
[0071] FIGS. 7A-7C are schematic diagrams illustrating filter
channels of various layout patterns of the filter device of the
disposable cell separation apparatus shown in FIG. 2;
[0072] FIG. 8 is a schematic diagram illustrating filter channels
in parallel of the filter device of the disposable cell separation
apparatus shown in FIG. 2;
[0073] FIGS. 9A and 9B are schematic diagrams illustrating a single
layer filter membrane and multilayer filter membrane of the filter
device of the disposable cell separation apparatus shown in FIG.
2;
[0074] FIG. 10 is a schematic diagram illustrating usage of the
disposable cell separation apparatus according to the second
embodiment of the present disclosure; and
[0075] FIGS. 11A and 11B are schematic diagrams illustrating
connections of the components of the disposable cell separation
apparatus shown in FIG. 10.
DETAILED DESCRIPTION
[0076] The present disclosure will be described below with
reference to the accompanying drawings, in which the drawings
illustrate several embodiments of the present disclosure. However,
it should be understood that the present disclosure can be
presented in many different ways, and is not limited to the
embodiments described below. In fact, the embodiments described
below are intended to make the disclosure of the present disclosure
more complete and fully explain the protection scope of the present
disclosure to those skilled in the art. It should also be
understood that the embodiments disclosed herein can be combined in
various ways to provide more additional embodiments.
[0077] It should be understood that in all the drawings, the same
reference numerals denote the same elements. In the drawings, the
dimensions of certain features may be deformed for clarity.
[0078] It should be understood that the terms in the specification
are only used to describe specific embodiments and are not intended
to limit the present disclosure. Unless otherwise defined, all
terms (including technical terms and scientific terms) used in the
specification have the meanings commonly understood by those
skilled in the art. For brevity and/or clarity, well-known
functions or structures may not be described in detail.
[0079] The singular forms "a", "the" and "this" used in the
specification include plural forms unless clearly indicated. The
terms "including", "comprising" and "containing" used in the
specification indicate the presence of the claimed feature, but do
not exclude the presence of one or more other features. The term
"and/or" used in the specification includes any and all
combinations of one or more of the related listed items. The terms
"between X and Y" and "between about X and Y" used in the
specification should be interpreted as including X and Y. The term
"between about X and Y" used in this specification means "between
about X and about Y", and the term "from about X to Y" used in this
specification means "from about X to about Y".
[0080] In the specification, when an element is referred to as
being "on", "attached" to another element, "connected" to another
element, "coupled" to another element, or "contacting" another
element, etc., the element may be directly on another element,
attached to another element, connected to another element, coupled
to another element, or contacting another element, or an
intermediate element may be present. In contrast, it is said that
an element is "directly on" another element, "directly attached" to
another element, "directly connected" to another element, "directly
coupled" to another element, or "directly contacting" another
element, there will be no intermediate element. In the
specification, when an element is arranged "adjacent" to another
element, it may mean that the element has a portion overlapping
with an adjacent element or a portion located above or below the
adjacent element.
[0081] In the specification, terms such as "upper", "lower",
"left", "right", "front", "rear", "high", "low", etc., can describe
the relationship of one element and another element in the
drawings. It should be understood that, in addition to the
orientation shown in the drawings, the terms describing spatial
relationships also indicate different orientations of the device in
use or operation. For example, when the device in the drawings is
turned upside down, elements that were originally described as
being "below" other elements may now be described as being "above"
other elements. The device can also be oriented in other ways
(e.g., rotated by 90 degrees or in other orientations), and the
relative spatial relationships will be explained accordingly.
[0082] FIG. 1 is a schematic diagram illustrating a disposable cell
separation apparatus 2. The cell separation apparatus 2 may be
configured to separate or remove specific constituent components
(such as cells) of a liquid (such as a culture fluid) in the
bioreactor 1. As shown in the figure, the cell separation apparatus
2 may include a power device 3, a liquid buffer device 4, a valve
device 5, and a filter device 6. The liquid buffer device 4 and the
bioreactor 1, the filter device 6 and the bioreactor 1, and the
liquid buffer device 4 and the filter device 6 may be in fluid
connection via liquid pipelines. The power device 3 and the liquid
buffer device 4 may be in fluid connection via a gas pipeline. The
power device 3 may be configured to drive the liquid to leave the
bioreactor 1, and enter the liquid buffer device 4 and the filter
device 6, and finally be discharged. The liquid buffer device 4 may
be configured to temporarily receive the liquid leaving the
bioreactor 1, so that the liquid in the entire flow path flows
smoothly without generating back and forth pressure fluctuations.
The valve device 5 may be configured to control the opening and
closing of the liquid pipelines. The filter device 6 may be
configured to separate, for example, cells and culture fluids.
[0083] FIG. 2 is a schematic diagram illustrating usage of the
disposable cell separation apparatus 2 according to a first
embodiment of the present disclosure, FIGS. 3A and 3B are schematic
diagrams illustrating connections of components of the disposable
cell separation apparatus 2, and FIGS. 4A and 4B show an exploded
stereogram and an exploded perspective view illustrating the
disposable cell separation apparatus 2, and FIG. 4C is an exploded
perspective view illustrating the disposable cell separation
apparatus 2 without related power device. As shown in the figure,
the liquid buffer device 4, the valve device 5 and the filter
device 6 may be integrated in the box body 8 and arranged from a
first end of the box body 8 to an opposite second end. The liquid
buffer device 4 and the filter device 6 may be connected by a
liquid pipeline disposed in the box body 8, and the valve device 5
may be disposed in the liquid pipeline. The power device 3 may be
fixed to the first end of the box body 8 by various known methods
(such as screw connection, welding, shape fitting, etc.), and in
fluid connection with the liquid buffer device 4. The length of the
box body 8 from the first end to the second end may be in a range
from 1 cm to 8 cm, the width may be in a range from 1 cm to 15 cm,
and the height may be in a range from 1 cm to 15 cm.
[0084] The liquid buffer device 4 may include two side-by-side
liquid cavities 40L and 40R disposed near the first end of the box
body 8. Each of the liquid cavities 40L and 40R may receive liquid
inside the cavity. In some embodiments, each of the liquid cavities
40L and 40R may be of a rectangular or a cube shape, and include an
inner wall facing the valve device 5 and the filter device 6, an
opposite outer wall, and a side wall connecting the inner wall and
the outer wall. The liquid cavity 40L may include air holes
disposed on the side wall or the outer wall, and a liquid inlet and
an outlet disposed on the inner wall. The air holes may be in fluid
communication with the power device 3, the liquid inlet may be in
fluid communication with the bioreactor 1 through a liquid channel
72L disposed on the box body 8 and a separate liquid conduit (not
shown). The liquid outlet may be in fluid communication with the
filter device 6 through a liquid channel 73L disposed on the box
body 8.
[0085] The power device 3 may be a device capable of driving gas to
reciprocate, including, for example, a syringe pump, an air
cylinder, or the like. Gas (for example, the air) may exist between
the power device 3 and the liquid surface inside the liquid cavity
40L. The power device 3 may pump gas out of the liquid cavity 40L
through the air holes of the liquid cavity 40L, and generate a
negative pressure in the liquid cavity 40L, thereby pumping the
liquid in the bioreactor 1 into the liquid cavity 40L through the
separate liquid conduit, the liquid channel 72L, and the liquid
inlet. The power device 3 may further push the gas into the liquid
cavity 40L through the air holes of the liquid cavity 40L, and
generate a positive pressure in the liquid cavity 40L, thereby
pushing the liquid in the liquid cavity 40L to the filter device 6
through the liquid outlet and the liquid channel 73L to perform
filtering. The power device 3 may use gas to generate a driving
force and a drain force, thereby greatly reducing the damage to
cells caused by other methods (such as peristaltic pumps or
centrifugal pumps). Studies have shown that if the peristaltic pump
circulates for more than 30 hours, the cell viability may decrease
significantly.
[0086] The structure and function of the liquid cavity 40R may be
substantially the same as or similar to those of the liquid cavity
40L, and correspondingly, the liquid cavity 40R may include one or
more air holes, a liquid inlet and a liquid outlet. The air hole(s)
may be in fluid communication with the power device 3, the liquid
inlet may be in fluid communication with the bioreactor 1 through a
liquid channel 72R disposed on the box body 8 and a separate liquid
conduit (not shown), and the liquid outlet may be in fluid
communication with the filter device 6 through a liquid channel 73R
disposed on the box body 8. Similarly, the power device 3 may push
the liquid of the bioreactor 1 into the liquid cavity 40R and out
of the liquid cavity 40R using gas.
[0087] The volumes of the liquid cavities 40L and 40R may be
determined based on a flow rate of the filter device 6, and may
generally be 0.01-0.8 bioreactor culture volume. Maximum liquid
volumes in the liquid cavities 40L and 40R may account for 40%-80%
volume of the liquid cavity to ensure a certain buffering and
prevent the liquid from contacting the downstream filter device 6
when the liquid is suctioned. In some embodiments, a liquid level
sensor may be installed in the liquid cavities 40L and 40R to
determine the action time of the positive pressure and the negative
pressure.
[0088] In addition to the liquid cavities 40L and 40R, the box body
8 may further include a first shell plate 81, a membrane layer 82,
a support plate 83, and a second shell plate 84 that stack on each
other. The liquid channels 72L, 73L, 72R, 73R, the valve device 5,
and the filter device 6 may be disposed between the stacked layer.
The liquid cavities 40L and 40R may be fixed to an outer end
surface of the stacked layer in various ways (for example, by
ultrasonic welding, bonding, etc.).
[0089] The liquid channels 72L, 73L, 72R, and 73R may be configured
as micro channels, and may be recessed from an inner surface of the
first shell plate 81, and a top of the liquid channels 72L, 73L,
72R, and 73R may be covered and sealed by a sealing film 74 in the
membrane layer 82. The inlets of the liquid channels 72L and 72R
may be exposed on a side wall of the box body 8, or configured as
through holes on the support plate 83 and the second shell plate
84, and in fluid communication with the bioreactor 1 through one or
more liquid conduits, and the outlets of the liquid channels 72L
and 72R may be respectively connected to the liquid inlet of the
cavity 40L and the liquid inlet of the liquid cavity 40R. The
inlets of the liquid channels 73L and 73R may be respectively
aligned and connected to the outlet of the liquid cavity 40L and
the outlet of the liquid cavity 40R, and the outlets of the liquid
channels 73L and 73R may be in fluid connection with the filter
device 6. In some embodiments, the liquid channels 72L, 73L, 72R,
and 73R may be configured on the first shell plate 81 by machining,
laser etching, soft plastic injection molding, or the like. In some
embodiments, a cross section (that is perpendicular to the first
shell plate 81) of the liquid channels 72L, 73L, 72R, 73R may be of
a shape of a semicircle or rectangle, and a diameter or a side
length of the liquid channels may be in a range from 0.01 mm to 2
mm, and more particularly from 0.1 mm to 1 mm. In some embodiments,
one or more pressure sensors may be installed in the liquid
channels 72L, 73L, 72R, and 73R to monitor whether the filter
device 6 is clogged.
[0090] The valve device 5 may be configured to control opening and
closing of the liquid channels. As shown in the figure, for the
liquid cavity 40L, the valve device 5 may include an inlet valve
52L disposed in the liquid channel 72L, and an outlet valve 53L
disposed in the liquid channel 73L. When the power device 3 pumps
the gas out from the liquid cavity 40L, the inlet valve 52L may be
opened and the outlet valve 53L may be closed, so that the liquid
in the bioreactor 1 is suctioned into the liquid cavity 40L through
the liquid channel 72L. When the power device 3 pushes the gas into
the liquid cavity 40L, the inlet valve 52L may be closed and the
outlet valve 53L may be opened, so that the liquid in the liquid
cavity 40L is pushed to the filter device 6 through the liquid
channel 73L for filtering.
[0091] Similarly, for the liquid cavity 40R, the valve device 5 may
include an inlet valve 52R disposed in the liquid channel 72R, and
an outlet valve 53R disposed in the liquid channel 73R. When the
power device 3 pumps the gas out from the liquid cavity 40R, the
inlet valve 52R may be opened and the outlet valve 53R may be
closed, so that the liquid in the bioreactor 1 is suctioned into
the liquid cavity 40R through the liquid channel 72R. When the
power device 3 pushes the gas into the liquid cavity 40R, the inlet
valve 52R may be closed and the outlet valve 53R may be opened, so
that the liquid in the liquid cavity 40R is pushed to the filter
device 6 through the liquid channel 73R for filtering.
[0092] The structures of the inlet valve 52L, the outlet valve 53L,
the inlet valve 52R and the outlet valve 53R may be substantially
the same or similar. In the following descriptions, the inlet valve
52L is taken as an example to illustrate the structure of the
valve, but it should be understood that the same or similar
structure is also applicable to the outlet valve 53L, the inlet
valve 52R, and the outlet valve 53R. The inlet valve 52L may
include a valve body cavity 521L and a spool cavity 522L. The valve
body cavity 521L may be disposed in the liquid channel 72L. Similar
to the structure of the liquid channel 72L, the valve body cavity
521L may be recessed from an inner surface of the first shell plate
81, and a top of the valve body cavity 521L may be covered and
sealed by the sealing film 74 in the membrane layer 82. In some
embodiments, a cross section of the valve body cavity 521L
perpendicular to the first shell plate 81 may be larger than a
cross section of the liquid channel 72L. The cross section of the
valve body cavity 521L along a direction perpendicular to the first
shell plate 81 may be of a circular, oval, square, rectangular, or
any suitable shape. In some embodiments, the valve body cavity 521L
may be configured on the first shell plate 81 by machining, laser
etching, soft rubber injection molding, or the like. The spool
cavity 522L may be a through cavity disposed on the support plate
83 and the second shell plate 84, and the position of the spool
cavity 522L may correspond to the valve body cavity 521L. The power
device 9 (for example, an air cylinder, etc.) may be in fluid
communication with the spool cavity 522L. The power device 9 may
push gas into the spool cavity 522L, and generate a positive
pressure in the spool cavity 522L, thereby pushing the sealing film
74 to seal the valve body cavity 521L and close the liquid channel
72L. The power device 9 may further suction gas out from the spool
cavity 522L, and generate a negative pressure in the spool cavity
522L, thereby causing the sealing film 74 to release the valve body
cavity 521L to open the liquid channel 72L. The power device 9 may
be fixed to the box body 8 (for example, the second shell plate 84
of the box body 8) by various known methods (such as screw
connection, welding, shape matching, etc.).
[0093] In some embodiments, as shown in FIGS. 5A and 5B, and FIGS.
6A and 6B, a spool 523L may be disposed in the spool cavity 522L,
and may be driven by the power device 9 to reciprocate into and out
of the valve body cavity 521L. The spool 523L may be of a
substantially cylindrical shape or a capsule shape. When the spool
523L enters the valve body cavity 521L, the valve body cavity 521L
may be closed to close the liquid channel 72L; when the spool 523L
leaves the valve body cavity 521L, the valve body cavity 521L may
be released to open the liquid channel 72L.
[0094] Referring back to FIGS. 2 to 4C, the filter device 6 may
include a filter channel 61, a filter membrane 62 and a collection
chamber 63. An inlet of the filter channel 61 may be in fluid
connection with a confluence of the liquid channels 73L and 73R to
receive, from the liquid cavities 40L and 40R, at different times,
the liquid to be filtered, and an outlet of the filter channel 61
may be closed or the filter channel 61 may form a closed loop.
Similar to the liquid channels 72L, 73L, 72R, 73R, the filter
channel 61 may be configured as a microfluidic channel and recessed
from an inner surface of the first shell plate 81 and a top of the
filter channel 61 may be covered by the filter membrane 62 in the
membrane layer 82. In some embodiments, the filter channel 61 may
be configured on the first shell plate 81 by mechanical processing,
laser etching, soft plastic injection molding, or the like.
[0095] In some embodiments, a cross section (that is perpendicular
to the first shell plate 81) of the filter channel 61 may be of a
semicircular or rectangular shape, and a diameter or a side length
of the filter channel may be in a range from 0.01 mm to 2 mm, and
more particularly from 0.1 mm to 1 mm, to match the flow rate of
the liquid. Because the diameter of the filter channel 61 is
relatively small, and the filter channel 61 is relatively long and
narrow, the liquid in the filter channel 61 may be in a laminar
high-speed flow state (the flow rate is, for example, 2 cm/s-100
cm/s), and the filter membrane 62 may be flushed, thereby
effectively improving the service life of the filter membrane 62.
Because the filtration direction is perpendicular to the liquid
flow direction, a tangential flow filtration may be provided.
[0096] As shown in FIGS. 7A-7C, an arrangement pattern of the
filter channel 61 on the first shell plate 81 may be designed into
various forms. In some embodiments, the pattern of the filter
channel 61 may be of a coiled shape to make full use of the area of
the filter membrane 62. Taking liquid resistance factor into
account, a length of a single filter channel 61 may be in a range
from 20 cm to 1000 cm, and more particularly, from 10 cm to 50
cm.
[0097] In some embodiments, as shown in FIG. 8, the filter channel
61 may be configured as a plurality of filter channels connected in
parallel, and the main inlet of the parallel filter channels 61 may
be connected to the confluence of the liquid channels 73L and 73R,
and the outlet of the parallel filter channels 61 may be closed or
the parallel filter channels 61 may form a closed loop. Each filter
channel 61 may be equipped with a filter valve 67 to coordinate to
open or close the filter channel 61. In a perfusion production
process, the filter valves 67 may be opened one by one or opened
simultaneously in accordance with different processes, and the
requirements of liquid exchange volume and culture time. The
structures of the filter valve 67 and the inlet valve 52L may be
substantially the same, and the description will not be repeated
herein.
[0098] Referring back to FIGS. 2 to 4C, the filter membrane 62 may
be supported by the support plate 83 to increase the strength of
the filter membrane 62 when the liquid presses the filter membrane
62. The support plate 83 may be equipped with a plurality of
through holes 64 on a site corresponding to the filter channel 61,
and thus, the filtered liquid can flow into the collection chamber
63 disposed on the second shell plate 84 through the through holes
64 on the support plate 83. As shown in FIGS. 9A and 9B, the filter
membrane 62 may be configured as a single layer or multiple layers.
In some embodiments, the filter membrane 62 may be configured as
multiple layers, each layer of the filter membrane may be supported
by a support plate 83, and each layer of the filter membrane may
have corresponding micro flow channel, thereby increasing the
filtration capacity and making it suitable for a relatively large
volume tank.
[0099] Referring back to FIGS. 2 to 4C, the collection chamber 63
may be recessed from an inner surface of the second shell plate 84,
and the position of the collection chamber 63 may correspond to a
plurality of through holes 64 on the support plate 83. The
collection chamber 63 may be equipped with a liquid outlet open to
the outside of the second shell plate 84, and the liquid may be
discharged through a return conduit 65. Thus, the filtered liquid
in the collection chamber 63 may be discharged from the culture
system. In some embodiments, a peristaltic pump or a pinch valve 66
may be disposed on the return conduit to control the flow rate of
the liquid backwashing the filter membrane 62.
[0100] In some embodiments, the filter membrane 62 may be made of a
material including, for example, PTFE, PP, PC, nylon, PES, PVDF, or
a sintered porous material. The filter membrane 62 may be treated
with hydrophilicity and/or positive charge, so that it is not easy
to adsorb cells that can block the filter membrane 62. The filter
membrane 62 may adopt a variety of pore sizes (including, for
example, 0.2 .mu.m, 1 .mu.m, 4 .mu.m, 5 .mu.m, 10 .mu.m, 20 .mu.m,
50 .mu.m, 200 .mu.m, etc.) according to different biological
processes (such as stem cells, tumor cells, CHO cells, microcarrier
processes, etc.). The support plate 83 may be made of a material
including, for example, PS, PMMA, PETG, PET and any other mesh
material, or may be a machined product of these materials. The
support plate 83 may be configured as a single layer or multiple
layers.
[0101] The operation process of the disposable cell separation
apparatus 2 according to the first embodiment of the present
disclosure may be described below. In some embodiments, the flow
direction of the liquid may be cyclic, i.e., the outflow of the
liquid in the bioreactor 2 and the inflow of the liquid to the
bioreactor 2 may be conducted by two pipelines, and the liquid in
each pipeline may flow in one direction. First, as shown in FIG.
3A, the inlet valve 52L may be opened, the outlet valve 53L may be
closed, the power device 3 may suction gas out from the liquid
cavity 40L, and thus, the liquid in the bioreactor 1 may be
suctioned into the liquid cavity 40L. After the liquid reaches a
preset scale of the liquid cavity 40L, the inlet valve 52L may be
closed and the outlet valve 53L may be opened. As shown in FIG. 3B,
the power device 3 may reverse and use a positive pressure to push
the liquid out from the liquid cavity 40L, and push the liquid to
the filter device 6 through the liquid channel 73L. The liquid may
serpentinely flow in the tortuous filter channel 61, be filtered
through the filter membrane 62, and enter the collection chamber
63. Finally, the filtered liquid may be drained through the return
conduit 65.
[0102] The operating states of the inlet valve 52R and outlet valve
53R on the side of the liquid cavity 40R may be exactly opposite to
those of the inlet valve 52L and the outlet valve 53L on the side
of the liquid cavity 40L. As shown in FIG. 3A, when the power
device 3 suctions the liquid into the liquid cavity 40L through a
negative pressure, the inlet valve 52R may be closed and the outlet
valve 53R may be opened, and the power device 3 may use a positive
pressure to push the liquid out from the liquid cavity 40R, and
reach the filter device 6 through the liquid channel 73R. The
liquid may serpentinely flow in the tortuous filter channel 61, be
filtered through the filter membrane 62, and enter the collection
chamber 63. Finally, the filtered liquid may be drained through the
return conduit 65. As shown in FIG. 3B, when the power device 3
uses a positive pressure to push the liquid out from the liquid
cavity 40L, the inlet valve 52R may be opened and the outlet valve
53R may be closed, and the power device 3 may use a negative
pressure to suction gas out from the liquid cavity 40R, and thus,
the liquid in the bioreactor 1 may be suctioned into the liquid
cavity 40R by using a negative pressure.
[0103] The liquid cavities 40L and 40R may cooperate with each
other repeatedly and periodically, so that the liquid can be
continuously pumped from the bioreactor 1 to the filter device 6.
Compared with the reciprocating movement of a single liquid cavity,
the using of the two liquid cavities may make the flow in the
entire pipeline smooth without generating back and forth pressure
fluctuations.
[0104] Hereinafter, a schematic diagram of a disposable cell
separation apparatus 1002 according to a second embodiment of the
present disclosure will be described with reference to FIGS. 10,
11A, and 11B. The cell separation apparatus 1002 may indicate the
same or similar structure in the cell separation apparatus 2. The
reference number of the cell separation apparatus 2 plus 1000 may
correspond to a reference number of the cell separation apparatus
1002. The cell separation apparatus 1002 may include a liquid
buffer device 1004 and a filter device 1006. The filter device 1006
and the bioreactor 1001, and the liquid buffer device 1004 and the
filter device 1006 may be in fluid connection through one or more
liquid pipelines. The power device 1003 and the liquid buffer
device 1004 may be in fluid connection through one or more gas
pipelines. The power device 1003 may be configured to drive the
liquid to leave the bioreactor 1001, and enter the liquid buffer
device 1004 and the filter device 1005, and finally be
discharged.
[0105] The liquid buffer device 1004 and the filter device 1006 may
be integrated on the box body 1008, and be disposed from a first
end of the box body 1008 to an opposite second end. The liquid
buffer device 1004 and the filter device 1006 may be in a fluid
connection through a liquid pipeline disposed on the box body 1008.
The power device 1003 may be fixed to a first end of the box body
1008 by various known methods (such as screw connection, welding,
shape matching, etc.), and be in fluid connection with the liquid
buffer device 1004.
[0106] The liquid buffer device 1004 may include a single liquid
cavity 1040 disposed near the first end of the box body 1008. The
liquid cavity 1040 may receive liquid inside the cavity. In some
embodiments, the liquid cavity 1040 may be of a rectangular
parallelepiped or a cube shape, and include an inner wall facing
the valve device 1005 and the filter device 1006, an opposite outer
wall, and a side wall connecting the inner wall and the outer
wall.
[0107] The liquid cavity 1040 may include one or more air holes
disposed on a side wall or an outer wall thereof, and a liquid port
disposed on an inner wall thereof. The air holes may be in fluid
communication with the power device 1003, and the liquid port may
be in fluid communication with the filter device 1006 through a
liquid channel 1073 disposed on the box body 1008. Gas (for
example, the air) may exist between the power device 1003 and the
liquid surface in the liquid cavity 1040. The power device 1003 may
suction the gas out from the liquid cavity 1040 through the air
holes, and generate a negative pressure in the liquid cavity 1040,
thereby suctioning the liquid in the bioreactor 1001 into the
liquid cavity 1040 through the filter device 1006, the liquid
channel 1073 and the liquid port. The power device 1003 may further
push the gas into the liquid cavity 1040 through the air hole(s),
and generate a positive pressure in the liquid cavity 1040, thereby
discharging the liquid in the liquid cavity 1040 through the liquid
port, the liquid channel 1073 and the filter device 1006.
[0108] Similar to the box body 8, in addition to the liquid cavity
1040, the box body 1008 may further include a first shell plate, a
membrane layer, a support plate, and a second shell plate that
stack on each other. A liquid channel 1073, a valve device 1005,
and a filter device 1006 may be disposed between the stacked layer.
The liquid cavity 1040 may be fixed to an outer end surface of the
stacked layer in various ways (for example, by ultrasonic welding,
bonding, etc.).
[0109] Similar to the liquid channel 73, the liquid channel 1073
may be configured as a micro channel and recessed from an inner
surface of the first shell plate, and a top of the liquid channel
may be covered and sealed by a sealing film in the membrane layer.
An inlet of the liquid channel 1073 may be aligned and connected to
the liquid port of the liquid cavity 1040, and an outlet of the
liquid channel may be in fluid communication with the filter device
1006. In some embodiments, the liquid channel 1073 may be
configured on the first shell plate by mechanical processing, laser
etching, soft plastic injection molding, or the like. In some
embodiments, a pressure sensor may be installed in the liquid
channel 1073 to monitor whether the filter device 1006 is
clogged.
[0110] The filter device 1006 may include a filter channel, a
filter membrane, and a collection chamber. The filter channel may
be configured as a microfluidic channel. An inlet of the filter
channel may be in fluid connection with the liquid channel 1073 to
receive the liquid to be filtered from the liquid cavity 1040. An
outlet of the filter channel may be closed or the filter channel
may form a closed loop. The structure of the filter device 1006 may
be similar to that of the filter device 6 in the first embodiment,
and the description will not be repeated herein.
[0111] The operation process of the disposable cell separation
apparatus 1002 according to the second embodiment of the present
disclosure will be described below. In some embodiments, the flow
of the liquid may be reciprocating, i.e., the outflow of the liquid
in the bioreactor 2 and the inflow of the liquid to the bioreactor
2 may be conducted by a single pipeline, and the liquid in the
pipeline may flow in two directions. First, as shown in FIG. 11A,
the power device 1003 may suction the gas out of the liquid cavity
1040, and thus, the liquid in the bioreactor 1001 may be suctioned
through the filter device 1006 and the liquid channel 1073 to the
liquid cavity 1040 by using a negative pressure. After the liquid
reaches a preset scale of the liquid cavity 1040, the power device
1003 may reverse and use a positive pressure to push the liquid out
from the liquid cavity 1040, and push the liquid through the liquid
channel 1073 to the filter device 1006. The liquid may serpentinely
flow in the tortuous filter channel, be filtered through the filter
membrane, and enter the collection chamber. Finally, the filtered
liquid may be drained through the return conduit.
[0112] Compared with a traditional cell separation apparatus, the
cell separation apparatus according to the embodiments of the
present disclosure may include a power system for filtering and
micro channels integrated in the cell separation apparatus that is
of a box shape, thereby reducing the volume and production cost
thereof.
[0113] The cell separation apparatus according to the embodiments
of the present disclosure may use a gas to generate a driving power
and/or a suction power of the liquid, thereby greatly reducing the
damage to cells caused by other methods (such as using peristaltic
pumps or centrifugal pumps).
[0114] The cell separation apparatus according to the embodiments
of the present disclosure may reduce the complexity and error-prone
nature of the traditional cell separation apparatuses caused by the
valve(s) and pipeline connection(s), thereby improving the
stability of the system.
[0115] The cell separation apparatus according to the embodiments
of the present disclosure may utilize the high-speed tangential
flow in the micro channel (the pore diameter of the micro channel
may be below 2 mm, and the flow rate is as high as 30 cm/s or
more), thereby greatly improving the service life of the filter
membrane. Because the cells in the pipeline are in laminar flow,
the turbulent shear force thereof may have no significant impact on
the cells. Because the filtering effect is greatly improved, the
cell separation apparatus according to the embodiments of the
present disclosure only needs a filter membrane with a very small
area, and the manufacturing cost may be greatly reduced with
respect to the hollow fiber column.
[0116] A micro channel switch may be integrated into the cell
separation apparatus according to the embodiments of the present
disclosure, and the opening and closing of the microfluidic channel
switch may be controlled by a membrane. The switching between the
logic of the power system and the multi-channels may be
conveniently controlled, thereby making the system flexible.
[0117] Although exemplary embodiments of the present disclosure
have been described, those skilled in the art should understand
that various changes and alterations can be made to the exemplary
embodiments of the present disclosure without substantially
departing from the spirit and scope of the present disclosure.
Therefore, all changes and alterations are included in the
protection scope of the present disclosure defined by the claims.
The present disclosure is defined by the appended claims, and
equivalents of these claims are also included.
* * * * *